2023
A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies
Chee C, Ooi M, Lee S, Sundar R, Heong V, Yong W, Ng C, Wong A, Lim J, Tan D, Soo R, Tan J, Yang S, Thura M, Al-Aidaroos A, Chng W, Zeng Q, Goh B. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Targeted Oncology 2023, 18: 391-402. PMID: 37060431, PMCID: PMC10192144, DOI: 10.1007/s11523-023-00962-w.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAdvanced solid tumorsFirst-in-human studyEuropean Leukemia NetworkSolid tumorsHematologic malignanciesTreatment-emergent adverse eventsHuman antibodiesDose-escalation cohortsDose-limiting toxicityGrade 2 vomitingPRL-3Refractory solid tumorsResponse Evaluation CriteriaSolid tumor patientsDose-expansion cohortReduced tumor growthFirst-in-humanPhase IStable diseaseStoma outputEvaluation CriteriaMyeloid leukemiaPharmacodynamic relationshipsAdverse events
2022
Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors
Lee M, Wong A, Ow S, Sundar R, Tan D, Soo R, Chee C, Lim J, Yong W, Lim S, Goh B, Wang L, Lee S. Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors. Targeted Oncology 2022, 17: 141-151. PMID: 35195837, PMCID: PMC8995271, DOI: 10.1007/s11523-022-00867-0.Peer-Reviewed Original ResearchConceptsHER2+ metastatic breast cancerDose-limiting toxicityMetastatic breast cancerBreast cancerSubcutaneous trastuzumabSolid tumorsConclusionsThe recommended phase II dosePharmacokinetic analysisRecommended phase II doseHER2+ breast cancerAdvanced solid tumorsPalliative systemic therapyMetastatic solid tumorsResultsThirty-seven patientsArea under the curveWeekly paclitaxelNeoadjuvant therapyStable diseaseFebrile neutropeniaPartial responseSystemic therapyMethodsEligible patientsEfficacy signalsElectrolyte disturbancesBiliary tract
2020
PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases
Kim G, Tan L, Sundar R, Lieske B, Chee C, Ho J, Shabbir A, Babak M, Ang W, Goh B, Yong W, Wang L, So J. PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases. Clinical Cancer Research 2020, 27: 1875-1881. PMID: 33148667, DOI: 10.1158/1078-0432.ccr-20-2152.Peer-Reviewed Original ResearchConceptsPressurized intraperitoneal aerosol chemotherapyPressurized intraperitoneal aerosolized chemotherapy proceduresPeritoneal cancer indexPeritoneal metastasisAerosol chemotherapyMedian peritoneal cancer indexPeritoneal Regression Grading ScoreRecommended phase II doseGrade 2 pancreatitisHighest-dose cohortPhase II doseDose-limiting toxicityFirst-line chemotherapyDose-escalation designTreat peritoneal metastasisPhase I studyImprove drug distributionII doseStable diseaseCancer indexMedian ageCohort expansionGastrointestinal tumorsPharmacokinetic analysisDose levelsPhase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers
Lee S, Shimasaki N, Lim J, Wong A, Yadav K, Yong W, Tan L, Koh L, Poon M, Tan S, Ow S, Bharwani L, Yap Y, Foo M, Coustan-Smith E, Sundar R, Tan L, Chong W, Kumarakulasinghe N, Lieow J, Koe P, Goh B, Campana D. Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers. Clinical Cancer Research 2020, 26: 4494-4502. PMID: 32522887, DOI: 10.1158/1078-0432.ccr-20-0768.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiopsyBreast NeoplasmsCoculture TechniquesCombined Modality TherapyDose-Response Relationship, DrugFemaleHumansImmunotherapyK562 CellsKiller Cells, NaturalMaleMiddle AgedReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsStomach NeoplasmsTransplantation, AutologousTrastuzumabConceptsAntibody-dependent cell cytotoxicityAutologous NK cellsNK cellsPhase I trialI trialNK cells expressed high levelsNatural killer (NK) cellsActivated autologous NK cellsHER2-positive solid tumorsPhase I dose escalationPeripheral blood NK cellsHER2-positive malignanciesNK cell infusionNK cell therapyBlood NK cellsNK cell expansionIncreased NK cellsPhase II trialPreliminary antitumor activityNK cell activityCells expressing high levelsHER2-positive cancersStable diseasePartial responseII trial
2018
A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer
Sundar R, Rha S, Yamaue H, Katsuda M, Kono K, Kim H, Kim C, Mimura K, Kua L, Yong W. A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer. BMC Cancer 2018, 18: 332. PMID: 29587677, PMCID: PMC5870101, DOI: 10.1186/s12885-018-4234-8.Peer-Reviewed Original ResearchConceptsAdvanced gastric cancerCytotoxic T lymphocytesGastric cancerCancer vaccinesOverall survivalAdverse eventsRecommended phase 2 doseMedian progression free survivalSpecific cytotoxic T lymphocytesTreatment-related adverse eventsAdvanced gastric cancer patientsPeptide cancer vaccinesPhase 2 dosePhase I/Ib studyPositive CTL responsesDose-limiting toxicityMedian overall survivalProgression free survivalInjection site erythemaOptimal dosing scheduleGastric cancer patientsSingle-arm trialPhase I/IbStable diseaseFree survival
2017
Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit
Sundar R, Custodio A, Petruckevich A, Chénard-Poirier M, Ameratunga M, Collins D, Lim J, Kaye S, Tunariu N, Banerji U, de Bono J, Lopez J. Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit. Clinical Oncology 2017, 30: 185-191. PMID: 29224898, DOI: 10.1016/j.clon.2017.11.011.Peer-Reviewed Original ResearchConceptsAdvanced biliary tract carcinomaPhase I clinical trialPhase I unitABC patientsAdvanced biliary tract cancerMolecular characterisation of tumoursClinical outcomes of patientsClinical benefit rateBiliary tract carcinomaBiliary tract cancerComprehensive molecular profilingPhase I trialOutcomes of patientsCharacterisation of tumoursStable diseaseI unitsAdvanced diseaseI trialBenefit rateTargeted therapyTreatment detailsTrial discontinuationExceptional respondersPTEN lossClinical outcomesAbstract 3081: Precision medicine for patients with advanced small cell lung cancer treated with novel therapeutic agents in a phase I clinical trials unit
Lim J, Harris S, Ameratunga M, Sundar R, Ang J, Collins D, Chénard-Poirier M, Garces A, Kaye S, Lopez J, Banerji U, Bono J, Yap T. Abstract 3081: Precision medicine for patients with advanced small cell lung cancer treated with novel therapeutic agents in a phase I clinical trials unit. Cancer Research 2017, 77: 3081-3081. DOI: 10.1158/1538-7445.am2017-3081.Peer-Reviewed Original ResearchSmall cell lung cancerAdvanced small cell lung cancerNovel therapeutic agentsRECIST SDStable diseasePD-1Partial responsePARP inhibitorsNovel therapiesAmerican Association for Cancer Research annual meetingsNext generation sequencingTherapeutic agentsSignals of antitumor activityNo dose limiting toxicitiesDNA damage repairClinical outcomes of patientsResponse to novel therapiesPD-1 inhibitorsPlatinum-sensitive diseaseRECIST partial responseRECIST stable diseaseDose-limiting toxicityTargeted next generation sequencingTumor molecular profilingPhase I trialWhole exome sequencing (WES) of multiple spatially distinct biopsies from single metastatic lesions to evaluate tumour heterogeneity and identify actionable truncal mutations (ATMs) in patients (pts) with advanced solid malignancies using a radiologically-guided single-pass percutaneous technique.
Heong V, Wee B, Goh S, Tay D, Lee X, Soo R, Lim J, Sundar R, Chee C, Lee S, Ow S, Goh B, Yong W, Wong A, Gopinathan A, Lim D, Pang B, Feroz M, Soong R, Tan D. Whole exome sequencing (WES) of multiple spatially distinct biopsies from single metastatic lesions to evaluate tumour heterogeneity and identify actionable truncal mutations (ATMs) in patients (pts) with advanced solid malignancies using a radiologically-guided single-pass percutaneous technique. Journal Of Clinical Oncology 2017, 35: 2550-2550. DOI: 10.1200/jco.2017.35.15_suppl.2550.Peer-Reviewed Original ResearchTumor mutational burdenWhole-exome sequencingMetastatic lesionsNSCLC ptsHigh tumor mutational burdenEvaluate tumor heterogeneityCheckpoint inhibitorsStable diseaseTumor shrinkageTruncal mutationsCore biopsyMutational burdenSolid malignanciesComplication rateNon-synonymous variantsTumor heterogeneityIntratumoral heterogeneitySubclonal diversityGenomic profilingPercutaneous techniquesExome sequencingMutational heterogeneityAkt inhibitorMedian amountPoor quality DNA